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Biochemically Recurrent Prostate CarcinomaPhase 2NCT04585932

Androgen Deprivation Therapy and Apalutamide With or Without Radiation Therapy for the Treatment of Biochemically Recurrent Prostate Cancer, RESTART Study

A Phase 2 study testing Apalutamide, Degarelix and Leuprolide Acetate in people with Biochemically Recurrent Prostate Carcinoma and Metastatic Prostate Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well androgen deprivation therapy and apalutamide with or without radiation therapy works for the treatment of prostate cancer that has a rise in the blood level of prostate-specific antigen (PSA) and has come back after treatment with surgery or radiation (biochemically recurrent). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Apalutamide, Degarelix and Leuprolide Acetate
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
24 Nov 2020to 8 Jan 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed prostate cancer
  • Signed informed consent form (ICF) indicating that the subject understands the purpose of, and procedures required for, the study and is willing to participate in the study
  • Consent to MD Anderson laboratory protocol Lab02-152
  • Available tumor tissue sample (recently collected +/- archival)
  • Biochemically recurrent prostate cancer following definitive treatment with radical prostatectomy or / and external beam radiation therapy. Patient may have received prior androgen deprivation with or without other treatments in the neoadjuvant, adjuvant or salvage setting as long as >= 6 months from discontinuation have elapsed at the time of randomization
  • Progression based on the following criteria:
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  • PSA progression: For patients with prior radical prostatectomy (+/- radiation), PSA progression defined by a minimum of two rising PSA levels with an interval of at least 1 week between each determination and a PSA of >= 0.5 ng/ml at screening. For patients with only prior definitive radiation of the prostate, PSA recurrence is defined as PSA >= nadir+2 ng/mL
  • PSA doubling time of =< 12 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values >= 0.1 ng/mL PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator
  • Identification of up to 5 metastatic lesions or/and pelvic node recurrent sites by advanced imaging technology (PSMA PET/CT or fluciclovine PET/CT). In case of inconsistency between the two imaging modalities, up to 5 lesions in the PSMA/PET will be accepted. All sites should be eligible to be treated with definitive intent. At least one of these lesions will be histologically confirmed. Symptomatic metastatic disease or disease impending symptoms (e.g. brain metastasis, painful bone metastasis, and spine disease) can be treated with definitive local therapy prior to enrollment. This lesion will be counted towards the total number of metastatic lesions
  • Must be able to receive luteinizing hormone-releasing hormone (LHRH) agonist or antagonist during the course of the study
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
  • Must be able to swallow tablets
  • To avoid risk of drug exposure through the ejaculate (even men with vasectomies), patients must agree while on study drug and for 3 months following the last dose of study drug to:
  • Use a condom during sexual activity
  • Not donate sperm
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Hemoglobin >= 9.0 g/dL
  • Platelet count >= 75 x 10^9/L
  • Serum albumin >= 3 g/dL
  • Calculated creatinine clearance >= 40 mL/min using the Cockcroft-Gault equation
  • Serum total bilirubin =<1.5 x upper limit of normal (ULN) or direct bilirubin =< 1.5 x ULN (Note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3.0 x ULN
  • Testosterone > 150 ng/dL. For patients treated with ADT with or without short-term first generation anti androgens (e.g. bicalutamide) up to 4 weeks prior to randomization, a testosterone measurement prior to the ADT treatment will be used to determine eligibility, and must have been > 150 ng/dL. If no testosterone level is available from before luteinizing hormone-releasing hormone analogue (LHRHa) injection and within 6 weeks of randomization, the patient will be ineligible

Who cannot join

  • Histologically confirmed recurrence in a prior definitively irradiated prostate cancer field per the judgment of the investigator
  • Ongoing androgen deprivation therapy (with or without short-term first generation anti-androgens) for > 4 weeks at the time of randomization
  • =< 30 days prior to cycle 1 day 1, patient had:
  • A transfusion (platelets or red blood cells)
  • Hematopoietic growth factors
  • An investigational agent (=< 30 days or 5 half-lives, whichever is longer)
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  • Major surgery
  • Active hematologic or solid malignancy other than prostate cancer with at least 30% chance of recurrence per investigator assessment; (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission)
  • Known allergies, hypersensitivity, or intolerance to apalutamide or LHRH agonist/antagonist or excipients
  • Current evidence of any of the following:
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption
  • Corrected QT interval by the Fridericia correction formula (QTcF) > 450 msec on the screening electrocardiogram (ECG)
  • History of clinically significant cardiovascular disease including, but not limited to:
  • Myocardial infarction or unstable angina =< 3 months prior to treatment initiation
  • Clinically significant cardiac arrhythmia
  • Pulmonary embolism, stroke =< 3 months prior to treatment initiation
  • Congestive heart failure (New York Heart Association class III-IV)
  • Known evidence of an active infection requiring systemic therapy such as human immunodeficiency virus (HIV), active hepatitis, or fungal infection
  • History of seizure disorder
  • Patients receiving medications known to lower the seizure unless discontinued or substituted at least 4 weeks prior to study entry. These medications include:
  • Aminophylline/theophylline,
  • Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone),
  • Bupropion,
  • Lithium,
  • Meperidine and pethidine,
  • Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine),
  • Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
  • Any contraindication that precludes use or radiotherapy for identified lesion treatment per the judgment of the investigator
  • Any condition for which, in the opinion of the investigator, participation would not in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase 2 Response Evaluation of Finite Systemic Therapy With Advanced Androgen Signaling Inhibition and Radiation Therapy for Oligorecurrent Prostate Cancer (RESTART)

This phase II trial studies how well androgen deprivation therapy and apalutamide with or without radiation therapy works for the treatment of prostate cancer that has a rise in the blood level of prostate-specific antigen (PSA) and has come back after treatment with surgery or radiation (biochemically recurrent). Androgens can cause the growth of prostate tumor cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Androgen deprivation therapy drugs, leuprolide or degarelix, work to lower the amount of androgen in the body, also preventing the tumor cells from growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy with apalutamide and androgen deprivation therapy may help to control prostate cancer that has come back in only a few (up to 5) spots in the body.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess PSA progression-free survival in both treatment arms.

SECONDARY OBJECTIVES:

  1. To assess time of recovery of serum testosterone in both treatment arms. II. To assess PSA progression-free survival and overall survival following testosterone recovery in both treatment arms.

III. To assess safety of androgen deprivation therapy (ADT) + apalutamide as well as ADT + apalutamide in combination radiation therapy.

IV. To assess the time to first new metastasis or local / pelvic recurrence in both treatment arms.

  1. To assess the impact of both treatment arms on quality of life. VI. To assess the impact of both treatment arms on metabolic syndrome parameters.

VII. To assess the impact of both treatment arms on bone density. VIII. To investigate the association of changes in repeat advanced imaging with outcome.

IX. To compare fluciclovine and prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

EXPLORATORY OBJECTIVE:

  1. To identify potential markers of response or resistance to the administered therapies.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive apalutamide orally (PO) once daily (QD) on days 1-28 and ADT consisting of leuprolide intramuscularly (IM) every 12 weeks or degarelix subcutaneously (SC) every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy (RT) between cycles 4-7 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 and 4 months.

Being tested
Apalutamide, Degarelix, Leuprolide Acetate, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApalutamideDrug

    Also called ARN 509, ARN-509, ARN509, Erleada

    Given PO

  • DegarelixDrug

    Also called FE200486, Firmagon

    Given SC

  • Leuprolide AcetateDrug

    Also called A-43818, Abbott 43818, Abbott-43818, Carcinil

    Given IM

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation

    Undergo RT

Study groups in NCT04585932
Study groupRoleWhat they receive
Group I (apalutamide, leuprolide, degarelix)Active comparatorPatients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Apalutamide; Drug: Degarelix; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Group II (apalutamide, leuprolide, degarelix, RT)ExperimentalPatients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo RT between cycles 4-7 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Apalutamide; Drug: Degarelix; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to prostate specific antigen (PSA) recurrence

    Will estimate with the 95% Bayesian credible interval.

    Measured: From treatment start with androgen deprivation therapy plus apalutamide until PSA recurrence (> 0.2 ng/ml) for patients who received surgery, or PSA >= nadir+2ng/mL for patients who received only prior definitive radiation of the prostate, up to 4 years

Secondary outcomes (14)

  1. Time to testosterone recovery

    Measured using the Kaplan-Meier method.

    Measured: From treatment start until testosterone > 150ng/dL, assessed up to 4 years

  2. Eugonadal time to PSA recurrence

    Defined as the time to PSA recurrence following testosterone recovery (> 150 ng/dL). Measured using the Kaplan-Meier method.

    Measured: Up to 4 years

  3. Overall survival

    Measured using the Kaplan-Meier method.

    Measured: Up to 4 years

  4. Incidence of adverse events

    Safety data will be summarized by treatment arm, category, grade and attribution. Measured by grade 2 or higher adverse events by Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 4 weeks after last dose of apalutamide

  5. Time to first new metastasis or local/pelvic recurrence

    Measured: Up to 4 years

  6. Patient reported outcomes (PRO)

    Patient reported outcomes assessed using the following questionnaires EuroQOL 5 Dimensional Questionnaire (EQ-5D-5L) - EuroQOL 5 Dimensional Questionnaire (EQ-5D-5L); Outcome measure is the index value. Range: -0.573 to 1.

    Measured: Up to 4 years

  7. Patient reported outcomes (PRO)

    Patient reported outcomes assessed using the following questionnaires European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC-C30): Outcome measure is a raw score, ranging from 0-100.

    Measured: Up to 4 years

  8. Patient reported outcomes (PRO)

    Patient reported outcomes assessed using the following questionnaires European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-ELD14 Outcome measure is a raw score, ranging from 0-100

    Measured: Up to 4 years

  9. Patient reported outcomes (PRO)

    Patient reported outcomes assessed using the following questionnaires Expanded Prostate Cancer Index Composite (EPIC-26): Results are presented in a standardized 0-100 scale.

    Measured: Up to 4 years

  10. Metabolic syndrome changes

    Laboratory parameters that will be measured during screening and active treatment (Lipid panel, blood sugar, HbA1c, Vitamin D, TSH, Testosterone, c-peptide, leptin) as well as measurements of weight and height and bone density measurement results will be used to evaluate changes in parameters predisposing to metabolic syndrome. .Laboratory parameters that will be measured during screening and active treatment (Lipid panel, blood sugar, HbA1c, Vitamin D, TSH, Testosterone, c-peptide, leptin) as well as measurements of weight and height and bone density measurement results

    Measured: Up to 4 years

  11. Change in bone density

    The results from bone density scanning (DXA scan) will be used to evaluate changes in bone density in the patient population

    Measured: Up to 4 years

  12. Imaging changes

    Association of changes between baseline and repeat advanced imaging with outcome will be performed, as well as comparison between fluciclovine and PSMA PET/CT modalities, including detection rates and correlation of detected disease volume at baseline with outcome. These changes will be evaluated in correlation with molecular characteristics explored through interrogation of archival and recurrent tissue samples , exosome, steroid and androgen metabolism. Association of changes between baseline and repeat advanced imaging with outcome will be performed, as well as comparison between fluciclovine and PSMA PET/CT modalities, including detection rates and correlation of detected disease volume at baseline with outcome. These changes will be evaluated in correlation with molecular characteristics explored through interrogation of archival and recurrent tissue samples , exosome, steroid and androgen metabolism.

    Measured: Up to 4 years

  13. Fluciclovine positron emission tomography/computed tomography (PET/CT) modality assessment

    Will estimate lesion detection rate based on fluciclovine and prostate-specific membrane antigen (PSMA) PET/CT modalities and the agreement between fluciclovine and PSMA PET/CT results will be assessed through McNemar test.

    Measured: Up to cycle 4, day 1 (each cycle = 28 days)

  14. PSMA PET/CT modality assessment

    Will estimate lesion detection rate based on fluciclovine and PSMA PET/CT modalities and the agreement between fluciclovine and PSMA PET/CT results will be assessed through McNemar test.

    Measured: Up to cycle 4, day 1 (each cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2020
  2. Study start24 Nov 2020
  3. Primary completion8 Jan 2021
  4. Study completion8 Jan 2021

Why it stopped: At the request of the ad interim Department Chairman due to PI is no longer at institution.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04585932
Sponsor's protocol ID
2019-1093
Other IDs
NCI-2020-02553, 2019-1093
Status last verified
Jan 2021
First submitted
19 May 2020
Last updated
20 Jan 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Apalutamide, Degarelix and Leuprolide Acetate in people with Biochemically Recurrent Prostate Carcinoma and Metastatic Prostate Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to prostate specific antigen (PSA) recurrence (time frame: From treatment start with androgen deprivation therapy plus apalutamide until PSA recurrence (> 0.2 ng/ml) for patients who received surgery, or PSA >= nadir+2ng/mL for patients who received only prior definitive radiation of the prostate, up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04585932.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.

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